The mechanisms whereby collagen, the major structural protein of all vertebrates, is degraded and removed is of great importance if we are to gain insight not only into the complex problems involved in tissue organization, growth and development but also into certain disease processes involving the skin and other organs. It is now evident that collagenase is the specific enzyme required for the initiation of collagen breakdown. It is also clear that other extracellular proteases may also take part in this process. The major objectives of these studies, then, are to obtain a detailed understanding of the mode of action of certain human and animal collagenases in addition to a number of other neutral proteases and the mechanisms involved for controlling their biosynthesis and subsequent activity. It is our particular aim to relate the information obtained in these investigations to human diseases in which alterations of the connective tissues are involved.